The overall objectives of this project include examination of the pathways of transport of four different classes of antibiotics (the penicillins, cephalosporins, aminoglycosides and clindamycin) into the interstitial fluid space of osteomyelitic bone and quantitation of their concentration in the interstitial fluid space of osteomyelitic bone. The fluid spaces of infected bone, including the plasma, interstitial and total water space, will be determined in two different stages of osteomyelitis: acute osteomyelitis and low grade sepsis about a methyl methacrylate implant comparable to that noted with an infection of a total joint arthroplasty. These objectives will be achieved by measuring the volume of distribution of appropriate tracer and indicator dilution methods. The ability of four antibiotics representing four different classes of antibiotics--the penicillins (benzyl penicillin), cephalosporins (cephradine), aminoglycosides (gentamicin), and clindamycin--to move across the capillary membrane in osteomyelitic bone will be quantitated. The different molecular weights, extent of protein binding and degrees of lipophilia exhibited by these four antimicrobials will permit evaluation of the influence of these parameters on transcapillary movement of antibiotics in osteomyelitis. The concentration of each antibiotic in the interstitial fluid space of osteomyelitic bone will be quantitated with a radionuclide assay and compared to the plasma concentration determined with a biological assay. A more thorough understanding of the transport of antibiotics into an infectious lesion will help in the selection of an agent from the many agents presently available. This information should provide a better understanding of the mechanisms of failure of antimicrobial therapy in the treatment of sepsis about an implant. Additionally, if a consistent relationship between the interstitial fluid and plasma concentration is established for various antibiotics, the clinician can accurately monitor antimicrobial therapy during treatment of a patient with osteomyelitis with plasma bioassay--a readily available and inexpensive technique.